Drug Mega-Doses May Induce Side Effects

While an earlier published rodent study showed that ultra-high doses of resveratrol (1565 milligram human dose), equivalent to 1500 bottles of wine or many dietary supplement capsules, successfully overcame the adverse effects of a high-fat diet, the lowest dose that genetically mimics a calorie restricted diet went undetermined, till now.

Now an authoritative gene array study, conducted by researchers at the William S. Middleton Memorial Veterans Hospital and Lifegen Technologies in Madison, Wisconsin, shows that a dose of resveratrol (rez-vair-aw-trawl) 343 milligrams per day (4.9 mg per kilogram of body weight) produces a gene activation profile similar to a calorie restricted diet. Supra-high doses (greater than 500 milligrams) are not required and may produce side effects.

Both calorie restriction and resveratrol have been shown to prolong the life of all life forms, ranging from single-cell organisms (yeast cells) to more complex forms of life (fruit flies, roundworms) and warm-blooded mammals (laboratory rats).

Consumers never heard that a far lower human equivalent dose than 1565 milligrams ( 360 milligrams) was employed with undisclosed success in a landmark rodent study published in 2006. The lower-dose data were never published. [Resveratrol improves health and survival of mice on a high-calorie diet. Nature 2006 Nov 16; 444: 337-42]

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Drawbacks of supra-high doses

"Once mega-doses of resveratrol (more than 500 mg) began to be employed, side effects like anemia, Achilles heel tendonitis, anxiety reactions, numbness in the fingers, began to be reported," says Bill Sardi, spokesperson for Longevinex (long-jev-in-ex), a leading brand resveratrol dietary supplement. "This is probably because resveratrol is a copper chelator and excessive chelation will impair the availability of copper which is needed for collagen formation and nerve regeneration," he says. "Resveratrol is relatively safe, but not absolutely safe at any dosage. There are drawbacks," he adds.

Some online suppliers of resveratrol pills, who have no medical training, irresponsibly recommend up to 7000 milligrams of resveratrol a day. There is also evidence that supra-high dose resveratrol inhibits the absorption of folic acid (vitamin B9), an essential nutrient needed for DNA repair. [European Journal Nutrition 46: 329-36, 2007] High doses have not been tested in humans for long-term use.

Advertising claims by resveratrol supplement makers that their pills exert greater stimulation of the Sirtuin 1 DNA-repair gene should also be regarded with caution since an animal study shows over-stimulation (greater than 7.5 fold) of this gene induces heart failure in animals. [Circulation Research 2007; 100: 1512-21]